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Extracellular Matrix in Ischemic Heart Disease, Part 4/4: JACC Focus Seminar
Nikolaos G Frangogiannis1, Jason C Kovacic2
1Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York.
Insights
Changes in the cardiac extracellular matrix (ECM) after myocardial ischemia and infarction impact heart function. The ECM plays a key role in inflammation, repair, and adverse remodeling, affecting clinical outcomes.
Area of Science:
- Cardiovascular Biology
- Extracellular Matrix Research
- Cardiac Pathophysiology
Background:
- Myocardial ischemia and infarction lead to cardiomyocyte loss and significant alterations in the cardiac extracellular matrix (ECM).
- These ECM changes traditionally were understood to affect the mechanical properties of the heart.
- Emerging evidence highlights the ECM's active role in biological pathways beyond structural changes.
Purpose of the Study:
- To review the multifaceted role of the cardiac ECM in ischemic and infarcted hearts.
- To explore the ECM's contribution to inflammatory and reparative processes.
- To elucidate the ECM's role in adverse cardiac remodeling and dysfunction.
Main Methods:
- Review of existing scientific literature and evidence.
- Analysis of studies focusing on ECM composition and function post-myocardial injury.
- Synthesis of data linking ECM alterations to biological pathways and clinical outcomes.
Main Results:
- Altered cardiac ECM significantly impacts not only structural integrity but also mediates inflammatory and reparative responses.
- ECM modifications are implicated in the pathogenesis of adverse cardiac remodeling following ischemia and infarction.
- These ECM changes contribute to overall cardiac dysfunction and poor clinical outcomes.
Conclusions:
- The cardiac extracellular matrix is a critical mediator in the response to myocardial ischemia and infarction.
- ECM alterations are central to the development of adverse remodeling and cardiac dysfunction.
- Understanding ECM's role is vital for developing strategies to improve outcomes in ischemic heart disease.
Abstract:
Myocardial ischemia and infarction, both in the acute and chronic phases, are associated with cardiomyocyte loss and dramatic changes in the cardiac extracellular matrix (ECM). It has long been appreciated that these changes in the cardiac ECM result in altered mechanical properties of ischemic or infarcted myocardial segments. However, a growing body of evidence now clearly demonstrates that these alterations of the ECM not only affect the structural properties of the ischemic and post-infarct heart, but they also play a crucial and sometimes direct role in mediating a range of biological pathways, including the orchestration of inflammatory and reparative processes, as well as the pathogenesis of adverse remodeling. This final part of a 4-part JACC Focus Seminar reviews the evidence on the role of the ECM in relation to the ischemic and infarcted heart, as well as its contribution to cardiac dysfunction and adverse clinical outcomes.
